The present invention relates generally to fluid delivery devices, and is particularly concerned with a wearable, self-contained drug infusion device that can be used to deliver a variety of medications, including but not limited to insulin, to a patient.
Diabetes is a chronic disease that is caused by both hereditary and environmental factors. It is characterized by the body""s inability to control glucose levels. Left untreated, it causes damage to the circulatory and nervous systems and results in organ failures, amputations, neuropathy, blindness and eventually death. It has been definitively shown that the cost of the complications related to diabetes significantly exceeds the cost of therapy. The Diabetes Control and Complications Trial (DCCT) was a ten-year study of 1400 patients to assess the benefits of close control of blood glucose levels. The study found that such close control provided 50% to 75% reductions in retinopathy, nephropathy, neuropathy and cardiovascular risk.
There are roughly 17.5 million people with diabetes in the United States and Europe, and about 60 million more worldwide. Roughly 35% of these people use insulin to maintain close control of their glucose levels. Proper control of blood glucose levels through programmed insulin injection or infusion allows a high quality of life and a life expectancy of an additional 35 to 40 years from diagnosis.
Currently, there are two principal modes of daily insulin therapy. The first mode includes syringes and insulin pens. These devices are simple to use and are relatively low in cost, but they require a needle stick at each injection, typically three to four times per day. The second is infusion pump therapy, which entails the purchase of an expensive pump that lasts for about three years. The initial cost of the pump is a high barrier to this type of therapy. From a user perspective, however, the overwhelming majority of patients who have used pumps prefer to remain with pumps for the rest of their lives. This is because infusion pumps, although more complex than syringes and pens, offer the advantages of continuous infusion of insulin, precision dosing and programmable delivery schedules. This results in closer glucose control and an improved feeling of wellness.
The typical patient on intensive therapy injects insulin to provide a basal level and then takes supplemental boluses prior to meals during the day. Those on infusion pumps program their pumps to mimic this type of delivery schedule. There are several existing or anticipated means of insulin therapy that a patient might consider.
The first are so-called oral agents that enhance the ability of the body to utilize insulin. Typical compounds include sulfonylureas, biguanides and thiazolidinediones. Oral agents are initially appropriate for Type 2 diabetics, whose bodies produce some insulin, although after a period of years these patients generally need to supplement with additional insulin. For Type 1 diabetics, the body does not produce insulin and these agents are not effective.
Once the oral agents are no longer effective, insulin is injected using syringes or multi-dose insulin pens. The syringe is the least expensive means of delivery, but many patients are willing to pay a premium for the convenience of the insulin pen.
A recent advance has been the development of extremely long-acting insulins. While regular insulins have a physiological onset in 10 minutes and peak activity in about 90 minutes, current long-acting insulins peak in roughly 8 hours. This type of insulin can be taken in the morning and can be accompanied by bolus delivery at meals. The alternative of simply taking all of one""s insulin requirement in basal delivery is believed by many to be therapeutically unsound. Insulin resistance is theorized to build as a result of high concentrations of insulin in the bloodstream, and as a result ever increasing amounts of insulin are necessary to control blood glucose levels. Unfortunately, the basal plus bolus profile still results in the same high and undesirable frequency of injections, typically four per day. Long-acting insulin does provide good therapy for those patients whose bodies benefit from supplemental basal insulin, but this is a temporary condition and simply delays a more rigorous insulin injection regimen for six months to two years.
As their interest in intensive therapy increases, users typically look to insulin pumps. However, in addition to their high cost (roughly 8 to 10 times the daily cost of syringe therapy) and limited lifetime, insulin pumps represent relatively old technology and are cumbersome to use. Also, from a lifestyle standpoint, the tubing (known as the xe2x80x9cinfusion setxe2x80x9d) that links the pump with the delivery site on the user""s abdomen is very inconvenient and the pumps are relatively heavy, making carrying the pump a bother.
A new method of insulin delivery currently undergoing development is pulmonary delivery. The principal issue with pulmonary delivery is criticality of dose, as pulmonary delivery is relatively inefficient and difficult to quantify. As a result, it will be difficult to keep blood glucose levels in control with this delivery form, although it may prove very useful as a supplement for bolus delivery at mealtime. The inefficiency of delivery (currently about 10%) significantly drives up the cost of pulmonary therapy. The implications of chronic inhalation of insulin are also unknown.
In summary, patients on oral agents eventually move to insulin, and existing pump therapy is very expensive. Interest in better therapy is on the rise,,accounting for the observed growth in pump therapy and increased number of daily injections. What is needed to fully meet this increased interest is a form of insulin delivery that combines the best features of daily injection therapy (low cost and ease of use) with those of the insulin pump (continuous infusion, precision dosing and programmable delivery schedules), and that avoids the disadvantages of each. This will allow a greater number of patients to have access to improved insulin therapy at lower cost.
Several attempts have been made to provide ambulatory or xe2x80x9cwearablexe2x80x9d drug infusion devices that are low in cost and convenient to use. Some of these devices are intended to be partially or entirely disposable. In theory, devices of this type can provide many of the advantages of an infusion pump without the attendant cost and inconvenience. Unfortunately, however, many of these devices cannot provide precise control over the flow rate of the drug at a low delivery cost, and are thus not compatible with dose-critical drugs such as insulin. In addition, devices that operate with fixed insulin flow rates may meet cost targets but still require bolus injections at mealtimes. Ultimately, therefore, these existing devices do not represent an optimal alternative to infusion pumps.
In accordance with the present invention, the disadvantages and limitations of the prior art are substantially avoided by providing a wearable, self-contained drug infusion device that is capable of achieving the precise flow rate control needed for dose-critical drugs such as insulin. In preferred embodiments of the invention, piezoelectrically-actuated valve or pump structures are used in combination with thermal flow sensors and closed-loop control circuits for providing the desired flow rate control. The miniaturization that is possible with each of these technologies allows the drug infusion device to have very small dimensions so that it can be worn by the user with a minimum of discomfort and inconvenience, while at the same time allowing for the close control over flow rate that is required for safe and effective delivery of insulin and other drugs. Preferred embodiments of the device have a two-part construction in which the more expensive electronic components are housed in a reusable portion and the fluid delivery components are housed in a separable disposable portion. This is advantageous not only in reducing the effective cost of the device to the user, but also in assuring sterility of the drug and preventing fluid contamination of the reusable portion by confining the fluid flow path to the disposable portion. Also, because control over the flow rate of the drug is carried out electronically, variable and/or programmable control over the flow rate is possible. This renders the device particularly suitable for those drugs (such as insulin) that require different delivery rates at different times for different patients.
In accordance with the first embodiment of the present invention, a wearable, self-contained device for delivering a liquid medication by continuous infusion into a patient comprises a disposable portion and a reusable portion that is removably connected to the disposable portion. The disposable portion comprises a housing, a reservoir in the housing for containing a supply of the liquid medication and for delivering the liquid medication under pressure, and a delivery cannula carried by the housing. A flow channel conducts the liquid medication from the reservoir to the delivery cannula. The reusable portion comprises a closed loop control circuit for maintaining a predetermined flow of liquid medication through the flow channel of the disposable portion. The infusion device also includes a flow control valve in at least one of the disposable and reusable portions for controlling the flow of liquid medication through the flow channel from the reservoir to the delivery cannula; an actuator in at least one of the disposable and reusable portions for actuating the flow control valve, the actuator being electrically connectable to the closed loop control circuit of the reusable portion; and a flow sensor in at least one of the disposable and reusable portions for sensing the flow of liquid medication through the flow channel of the disposable portion, the flow sensor being electrically connectable to the closed loop control circuit of the reusable portion.
In a particularly preferred implementation of the first embodiment of the invention, the reservoir comprises at least one Belleville spring element for pressurizing the liquid medication contained in the reservoir. In this embodiment, the flow control valve may comprise a fixed obstruction in the flow channel and a flexible membrane that is held in contact with the obstruction by the actuator, with such contact preventing liquid flow through the flow channel except when the actuator is energized by the control circuit. The actuator preferably comprises a piezoelectric element which, when energized by the control circuit, flexes to allow the membrane to separate from the obstruction so that the liquid medication can flow through the flow channel. The piezoelectric element is preferably energized in a pulsatile manner by the control circuit, so that the flow control valve is repeatedly opened and closed with a duty cycle that maintains a predetermined average flow rate of the liquid medication through the flow channel. The flow sensor preferably comprises a thermal emitter and a thermal detector, both of which are in thermal contact with the liquid medication flowing in the flow channel, with the thermal emitter being located upstream of the thermal detector relative to the direction of liquid flow in the flow channel. Preferably, at least one wall of the flow channel comprises a flexible membrane which forms an exposed face of the disposable portion that is brought into contact with the reusable portion when the disposable and reusable portions are connected together. In this embodiment, the actuator and flow sensor may be contained in the reusable portion and may operate through the flexible membrane of the disposable portion, so that the flow channel can remain sealed when the reusable portion is disconnected from the disposable portion.
In accordance with a second embodiment of the present invention, a wearable, self-contained device for delivering a liquid medication by continuous infusion into the skin of a patient is provided that is similar in overall construction to the embodiment described previously, except that the reservoir in the disposable portion is not required to deliver the liquid medication under pressure. The disposable portion of the device comprises the housing, a reservoir in the housing for containing a supply of the liquid medication, a delivery cannula carried by the housing, and a flow channel for conducting the liquid medication from the reservoir to the delivery cannula. As in the previously-described embodiment, a reusable portion of the device is removably connected to the disposable portion, and includes a closed loop control circuit for maintaining a predetermined flow of liquid medication through the flow channel of the disposable portion. In this embodiment, however, the infusion device further includes a pump in at least one of the disposable and reusable portions for pumping the liquid medication through the flow channel from the reservoir to the delivery cannula, the pump being electrically connectable to the closed loop control circuit; and a flow sensor in at least one of the disposable and reusable portions for sensing the flow of liquid medication through the flow channel, the flow sensor being electrically connectable to the closed loop control circuit.
In a particularly preferred implementation of an infusion device in accordance with the second embodiment of the invention, the pump is contained in the disposable portion and comprises a diaphragm pump that is driven by an actuator in at least one of the disposable and reusable portions. The actuator preferably comprises a piezoelectric element, which may be of the conventional disk type or of the cantilevered type. The diaphragm pump preferably comprises one or more check valves for restricting the flow of liquid medication to a single direction. As in the previously-described embodiment, the flow sensor preferably comprises a thermal emitter and a thermal detector, both of which are in thermal contact with the liquid medication flowing in the flow channel, with the thermal emitter being located upstream of the thermal detector relative to the direction of liquid flow in the flow channel. Preferably, at least one wall of the flow channel comprises a flexible membrane which forms an exposed face of the disposable portion that is brought into contact with the reusable portion when the disposable and reusable portions are connected together. In this embodiment, the flow sensor may be contained in the reusable portion and may operate through the flexible membrane of the disposable portion, so that the flow channel can remain sealed when the reusable portion is disconnected from the disposable portion.
In accordance with a further aspect of the present invention, a system for delivering a liquid medication by continuous infusion into or through the skin of a patient may comprise three separate components. The first component is a disposable portion comprising a housing, a reservoir in the housing for containing a supply of the liquid medication, a delivery cannula carried by the housing, and a flow channel for conducting the liquid medication from the reservoir to the delivery cannula. The second component is a reusable portion that is removably connectable to the disposable portion. The reusable portion contains electrical flow control circuitry for controlling the flow of liquid medication in the flow channel of the disposable portion in response to wireless control signals. The reusable and disposable portions, when connected to each other, constitute a wearable, self-contained infusion device. The third component is a wireless unit that is separate from the usable and disposable portions. The wireless unit transmits wireless control signals to the reusable portion to control the flow of liquid medication in the flow channel of the disposable portion.
In particularly preferred embodiments of a liquid medication delivery system in accordance with this aspect of the present invention, the wireless unit transmits either radio frequency or optical (e.g., infrared) signals to the reusable portion. The wireless unit preferably includes a keypad and a display device, and may also receive and display status information that is transmitted by the reusable portion. Examples of status information may include a flow rate of the liquid medication, an amount of time remaining until the reservoir in the disposable portion becomes empty, a quantity of liquid medication remaining in the reservoir of the disposable portion, a warning to the user that the flow rate of liquid medication in the disposable portion is incorrect, and an indication of a battery condition in the reusable portion.